Bacteriophage Protein Shows Antibiotic Potential

The T7 bacteriophage produces a protein that blocks Escherichia coli cell division and has the potential of being developed into an antibiotic-replacing drug.

T7 produces over 100 progeny per host cell in less than 25 minutes. If the T7 phage infection completes a successful growth cycle, it invariably culminates in disintegration of the host cell. Bacteriophages take over host cell resources primarily via the activity of proteins expressed early in infection. One such protein produced by the T7 phage is called Gp0.4 (gene product 0.4).

Investigators at Tel Aviv University (Israel) and their colleagues at Duke University (Durham, NC, USA) reported in the November 11, 2013, online edition of the journal, Proceedings of the National Academy of Sciences of the United States of America (PNAS) that Gp0.4 was a direct inhibitor of the E. coli filamenting temperature-sensitive mutant Z division protein.

They showed that a chemically synthesized Gp0.4 bound to purified filamenting temperature-sensitive mutant Z protein and directly inhibited its assembly in vitro. Consequently, expression of Gp0.4 in vivo was lethal to E. coli cultures and resulted in bacteria that were morphologically elongated. Furthermore, the inhibition of cell division by Gp0.4 enhanced the bacteriophage’s competitive ability by enabling them to maximize their progeny number by inhibiting escape of the daughter cells of the infected bacteria.

“Bacteria are infested with bacteriophages, which are their natural enemies and which in most cases destroy them,” said senior author Dr. Udi Qimron, professor of clinical microbiology and immunology at Tel Aviv University. “Ever since the discovery of bacteriophages in the early 20th century, scientists have understood that, on the principle of the "enemy of your enemy is your friend"; medical use could be made of phages to fight bacteria.”

“GP0.4 impedes cell division in the E. coli cell. With its capacity for cell division blocked, the bacterium continues to elongate until it dies,” said Dr. Qimron. “Potentially, this protein could be the ideal antibiotic.”
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